Peripheral neuropathy (PN) is the main side effect with cycles of paclitaxel at standard doses (175 mg/m2 for 21 days). Administration of a single high-dose paclitaxel (HDP) is a novel approach for the treatment of cancer. We have prospectively measured neurotoxicity induced by HDP during a phase I trial. Nineteen patients were treated with escalating doses of paclitaxel by 24-hour infusion. In our study, PN induced by HDP was moderate, reversible, and not dose limiting. Severe PN was seen in patients who had received previous neurotoxic chemotherapy, and caution on the administration of HDP in this setting is warranted.